Slow neurodegeneration and transmissible spongiform encephalopathies/prion diseases. Hypothesis: a cycle involving repeated tyrosine kinase A activation could drive the development of TSEs.

Neurons are specialised non-mitogenic cells. They cannot be replaced after damage, but most survive the lifetime of the individual. This is achieved by a very specialised process of repair and regeneration. During this process, a phase of degeneration in the distal end of the damaged neuron occurs in response to tyrosine kinase activation by nerve growth factor, which results in removal of neuronal detritus from within the cell membrane. As this phase is completed the activity of tyrosine kinase is modulated and the regeneration phase begins. It is postulated that normal prions play a part in the modulation of tyrosine kinase activity; that abnormal prion isoforms may be damaged in the process releasing a few fragments of prion PrP106-126 and that these stimulate release of nerve growth factor, which activates tyrosine kinase once more, setting up the vicious spiral of slow neurodegeneration found in the transmissible spongiform encephalopathies.